Domperidone in Secondary Progressive Multiple Sclerosis (SPMS)

University of Calgary

Status and phase

Completed

Phase 2

Conditions

Multiple Sclerosis, Secondary Progressive

Treatments

Drug: Domperidone

Study type

Interventional

Funder types

Other

Identifiers

NCT02308137

Domperidone_MS01

Details and patient eligibility

About

The purpose of this clinical trial is to determine if Domperidone in a dose of 40 mg daily can prevent worsening of walking ability in people secondary progressive MS. The number of participants in this study will be 62. A maximum of 75 people with secondary progressive MS will be included. Each patient will be followed for 12 months from inclusion. Domperidone is a medication which has been shown to increase levels of the hormone prolactin. The best understood function of prolactin is the stimulation of milk production in women after delivery. However, the increase in prolactin levels seen in patients treated with standard doses of Domperidone (in doses of up to 80mg per day) usually does not lead to clinical symptoms. Prolactin has been shown to improve myelin repair in mice. Domperidone therefore may also improve myelin repair in people with MS. Domperidone is currently approved in Canada to treat slow moving bowels and nausea, for instance in patients with Parkinson's Disease or Diabetes Mellitus, where too slowly moving bowels can cause constipation. Domperidone is available as a tablet that is usually taken four times per day. Doses up to 80mg per day may be used but we estimate that a dose of only 40mg daily will be needed to stimulate myelin repair. Domperidone is usually well tolerated.

Full description

Primary objective

To demonstrate non-futility of domperidone for reducing progression of disability, as measured with the timed 25 foot walk (T25FW), in secondary progressive Multiple Sclerosis (SPMS).

Secondary objectives

To assess the safety of domperidone in the study population for the duration of the study.
To assess the effect of domperidone on hand dexterity as measured with the 9HPT
To assess the effect of domperidone on cognition, as measured with the SDMT
To assess the effect of domperidone on health related quality of life, as measured with the MSQOL-54
To assess the effect of domperidone on fatigue, as measured with the MFIS
To establish the Simon-2-stage model as a study model in MS research. The application of this methodology to studies in progressive MS will have important consequences for the design and conduct of clinical and translational research in progressive MS, in particular for phase II trials in progressive MS

Enrollment

64 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

written informed consent obtained
with Multiple Sclerosis, and with secondary progressive disease course
screening Expanded Disability Status Scale (EDSS) score between 4.0 and 6.5 inclusive
screening timed 25 foot walk (average of two trials) lof 9 seconds or more

Exclusion criteria

Long QT interval, defined as corrected QT interval of more than 470 msec in men and more than 450 msec in women on baseline ECG
Patients with known long-QT syndrome
Patients with known ventricular arrhythmia
Patients with a known electrolyte disturbance
Patients undergoing treatment with drugs that increase the QTc interval
Patients undergoing treatment with drugs that inhibit CYP3A4, in particular: Ketoconazole, Fluconazole, Erythromycin, Clarithromycin, Ritonavir
Patients with a history of breast cancer or carcinoma in situ
Patients with known renal insufficiency
Patients with known allergy or other intolerability to domperidone
Patients currently using Fampridine or 4-aminopyridine
Patients planning to start Fampridine or 4-aminopyridine during the study period
Patients planning to start Baclofen or Tizanidine during the duration of the study
Patients planning to increase or decrease their dose of Baclofen or Tizanidine during the study period
Patients planning to receive treatment with Botulinum toxin in the leg muscles during the duration of the study
Patients with a significiant hepatic impairment
Patients with a prolactinoma
Patients in whom gastrointestinal stimulation could be dangerous
Patients using MAO inhibitors
Patients with a history of breast cancer
Pregnant or breast-feeding women